The overall objective of this multidisciplinary patient oriented Program Project is to determine the role of mitochondrial dysfunction in the pathogenesis of insulin resistance and other related metabolic disorders in humans. All three projects in the Program entail recruitment and characterization of patients with mitochondrial abnormalities for metabolic characterization and genetic studies. In the Clinical Core volunteer recruitment, and screening will be centralized. The Core will provide specialized clinical support for magnetic resonance and stable isotope infusion studies for each of the studies under this Program Project. By centralizing this core we will be able to provide the highest level of technical and clinical expertise required for these magnetic resonance infusion and clamp studies as well as increased efficiency by eliminating duplication. Specifcally this core will: (I) screen, recruit and perform hyperinsulinemic-euglycemic clamp studies in young lean insulin resistant offspring and age-weight-activity matched control subjects and patients with mt tRNA mutations for Projects 1, 2, 3, (II) screen and recruit patients with a known mitochondrial tRNA mutation that is associated with hypertension for projects 1, 2, 3 and (III)screen and recruit healthy elderly subjects for project 3. In addition this core will provide specialized clinical support for stable isotope infusion studies that will be performed inside the 4.0T magnetic resonance spectrometer in order to assess tissue specific rates of mitochondrial activitiy in muscle, liver and brain for Projects 1,2 & 3. This clinical core is thus an essential resource that is required to complete the research proposed in Projects 1,2 & 3.